Five years of renewal funding are sought to study the etiology of alcoholism from a developmental behavioral genetic perspective. We hypothesize that an inherited predisposition to alcoholism may be expressed in early adolescence as 1) personality characteristics, 2) psychophysiological markers, and 3) psychiatric disorder. Our findings to date indicate that these factors are a) strongly heritably, b) differentiate individuals with and without alcoholism, c) differentiate individuals with and without an alcoholic parent, and d) prospectively predict the early initiation of alcohol use in middle adolescence and early onset alcoholism in late adolescence. We have also found support for our hypotheses 2) that these phenotypic markers of liability influence alcoholism risk in part by increasing the likelihood that an individual is both exposed to and affected by experimental risk factors during adolescence, and 2) that gender may moderate the association between liability markers, environmental risk factors, and an alcoholic outcome. During the first six years of funding, 717 families consisting of a twin pair and their parents have completed a day-long, comprehensive assessment of their 1) mental health and substance use history, 2) personality (positive and negative emotionality and behavioral constraint), 3) psychophysiological markers (including brain potentials [P3 and EEG], ANS measures, eye-blink startle, and eye tracking), and 3) environmental factors (including family climate, peer group, and cognitive risk factors). At study intake, the twins were either age 11 (an age prior to experimentation with alcohol and drugs) or age 17 (an age that precedes the adoption of adult drinking patterns). At the time of renewal, two-thirds of these families will have completed their first in-person follow-up (FU1) assessment three years after study intake. During the next five years we propose to 1) complete FU1 (when the twins are 14 and 20), 2) initiate and complete FU2 (at ages 17 and 23), 3) initiate FU3 (at ages 20 and 26), 4) ascertain and complete intake assessments on an additional 200 families of 11 year old twins to increase ethnic diversity and statistical power, and 5) analyze the intake and FU data, comparing it to our parallel study of 666 male twin families. The primary analyses to be undertaken during this funding period involve: 1) assessing the effects of parental alcoholism, 2) univariate biometric analyses of the twin data, 3) multivariate biometric analyses aimed at exploring genotype-environment correlation, and 4) analysis of genotype-environment interaction effects.